Mental health during the COVID-19 pandemic: the importance of social support in midlife women.

OBJECTIVE: This study aimed to examine sex differences in factors associated with mood and anxiety in midlife men and women during the COVID-19 pandemic. METHODS: During a remote visit, 312 adults aged 40-60 years (167 female; 23.6% perimenopausal) from the Human Connectome Project in Aging completed PROMIS measures of depression, anxiety and anger/irritability; perceived stress; and questions about social support, financial stress and menopause stage. Multivariate linear regression models assessed sex differences in mental health and the association of social support, financial stress and menopause stage with mental health. RESULTS: Anxiety was higher in women than in men (b = 2.39, p = 0.02). For women only, decreased social support was associated with increased anxiety (b = -2.26, p = 0.002), anger/irritability (b = -1.89, p = 0.02) and stress (b = -1.67, p = 0.002). For women only, not having close family was associated with increased depressive symptoms (b = -6.60, p = 0.01) and stress (b = -7.03, p < 0.001). For both sexes, having children was associated with lower depressive symptoms (b = -3.08, p = 0.002), anxiety (b = -1.93, p = 0.07), anger/irritability (b = -2.73, p = 0.02) and stress (b = -1.44, p = 0.07). Menopause stage was unrelated to mental health. CONCLUSION: Social support, but not financial stress, influenced mental health during the COVID-19 pandemic at midlife, particularly for women.

Inflammatory Dietary Potential Is Associated with Vitamin Depletion and Gut Microbial Dysbiosis in Early Pregnancy.

Pregnancy alters many physiological systems, including the maternal gut microbiota. Diet is a key regulator of this system and can alter the host immune system to promote inflammation. Multiple perinatal disorders have been associated with inflammation, maternal metabolic alterations, and gut microbial dysbiosis, including gestational diabetes mellitus, pre-eclampsia, preterm birth, and mood disorders. However, the effects of high-inflammatory diets on the gut microbiota during pregnancy have yet to be fully explored. We aimed to address this gap using a system-based approach to characterize associations among dietary inflammatory potential, a measure of diet quality, and the gut microbiome during pregnancy. Forty-seven pregnant persons were recruited prior to 16 weeks of gestation. Participants completed a food frequency questionnaire (FFQ) and provided fecal samples. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) from the FFQ data. Fecal samples were analyzed using 16S rRNA amplicon sequencing. Differential taxon abundances with respect to the DII score were identified, and the microbial metabolic potential was predicted using PICRUSt2. Inflammatory diets were associated with decreased vitamin and mineral intake and a dysbiotic gut microbiota structure and predicted metabolism. Gut microbial compositional differences revealed a decrease in short-chain fatty acid producers such as Faecalibacterium, and an increase in predicted vitamin B12 synthesis, methylglyoxal detoxification, galactose metabolism, and multidrug efflux systems in pregnant individuals with increased DII scores. Dietary inflammatory potential was associated with a reduction in the consumption of vitamins and minerals and predicted gut microbiota metabolic dysregulation.

Inflammatory dietary potential is associated with vitamin depletion and gut microbial dysbiosis in early pregnancy.

Background: Pregnancy alters many physiological systems, including the maternal gut microbiota. Diet is a key regulator of this system and can alter the host immune system to promote inflammation. Multiple perinatal disorders have been associated with inflammation, maternal metabolic alterations, and gut microbial dysbiosis, including gestational diabetes mellitus, preeclampsia, preterm birth, and mood disorders. However, the effects of high inflammatory diets on the gut microbiota during pregnancy have yet to be fully explored. Objective: To use a systems-based approach to characterize associations among dietary inflammatory potential, a measure of diet quality, and the gut microbiome during pregnancy. Methods: Forty-nine pregnant persons were recruited prior to 16 weeks of gestation. Participants completed a food frequency questionnaire (FFQ) and provided fecal samples. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) from FFQ data. Fecal samples were analyzed using 16S rRNA amplicon sequencing. Differential taxon abundance with respect to DII score were identified, and microbial metabolic potential was predicted using PICRUSt2. Results: Inflammatory diets were associated with decreased vitamin and mineral intake and dysbiotic gut microbiota structure and predicted metabolism. Gut microbial compositional differences revealed a decrease in short chain fatty acid producers such as Faecalibacterium, and an increase in predicted vitamin B12 synthesis, methylglyoxal detoxification, galactose metabolism and multi drug efflux systems in pregnant individuals with increased DII scores. Conclusions: Dietary inflammatory potential was associated with a reduction in the consumption of vitamins & minerals and predicted gut microbiota metabolic dysregulation.

Melanoma literacy among the general population of three western US states.

Melanoma is a significant cause of cancer death, despite being detectable without specialized or invasive technologies. Understanding barriers to preventive behaviors such as skin self-examination (SSE) could help to define interventions for increasing the frequency of early detection. To determine melanoma knowledge and beliefs across three high-incidence US states, 15,000 surveys were sent to a population-representative sample. We aimed to assess (1) melanoma literacy (i.e., knowledge about melanoma risks, attitudes, and preventive behaviors) and (2) self-reported SSE and its association with melanoma literacy, self-efficacy, and belief in the benefits of SSE. Of 2326 respondents, only 21.2% provided responses indicating high knowledge of melanoma, and 62.8% reported performing an SSE at any time in their lives. Only 38.3% and 7.3% reported being "fairly" or "very" confident about doing SSE, respectively. SSE performance among respondents was most strongly associated with higher melanoma knowledge, higher self-efficacy, and personal history of melanoma. Melanoma literacy among survey respondents was modest, with greater literacy associated with a higher likelihood of reported preventive behavior. This assessment establishes a baseline and provides guidance for public health campaigns designed to increase prevention and early detection of this lethal cancer.

Effects of estrogen and progesterone on neuroactive steroids and cytokines in patients with suicidality.

BACKGROUND: In ovulating psychiatric patients experiencing suicidality, suicidal ideation (SI) often peaks perimenstrually. Our recent double-blind, placebo-controlled, crossover randomized clinical trial (RCT; NCT03720847) showed that perimenstrual administration of estradiol and progesterone (EP) can prevent this peak in SI and depressed mood. In this pre-registered follow-up analysis, we studied how the menstrual cycle and experimental manipulation affected two neurobiological systems associated with the menstrual cycle and suicide risk: GABAergic neuroactive steroids (NAS) and peripheral cytokines. METHODS: In 26 psychiatric outpatients with natural menstrual cycles and past-month SI, we analyzed serum samples from three blood draws (midluteal, perimenstrual, midfollicular) per experimental condition (EP vs placebo) timed to a luteinizing hormone-surge ovulation test. Using gas chromatography/mass spectrometry (GC/MS), we measured the progesterone (P4)-derived pregnane NAS (3α,5α)- 3-hydroxypregnan20-one (3α,5α-THP), (3α,5ß)- 3-hydroxypregnan-20-one (3α,5ß-THP), (3α,5α)- 3,21-dihydroxypregnan-20-one (3α,5α-THDOC), (3α,5α)- 3-hydroxyandrostan-17-one (3α,5α-A), the androstane NAS (3α,5ß)- 3-hydroxyandrostan-17-one (3α,5ß-A), (3α,5α,17ß)-androstane-3,17-diol (3α,5α-A-diol), (3α,5ß,17ß)-androstane-3,17-diol (3α,5ß-A-diol), and their precursor pregnenolone. High sensitivity multiplex assay kits quantified peripheral cytokines IL-1ß, IL-6, and TNF-α. RESULTS: P4-derived NAS fluctuated in parallel with P4 and increased with exogenous perimenstrual administration of EP. Conversely, androstane NAS either did not fluctuate or fluctuated inversely from P4, and these NAS decreased with exogenous EP. Peripheral cytokines did not show cyclical patterns, but each significantly predicted SI, depressed mood, or anxiousness. Concomitant SSRI medication use predicted lower androstane NAS. CONCLUSIONS: While preliminary and exploratory, our findings provide critical descriptive context for future studies. Further, our work presents menstrual cycle-related patterns for ten frequently-studied biomarkers, allowing for improved quality of comparisons involving naturally-cycling populations in research.

Using self-report RDoC measures to identify transdiagnostic translational targets for perinatal affective disorders.

Perinatal depression affects 6.5-12.9% of women, with high rates in women of color and comorbid perinatal anxiety in up to 50% of cases. The Research Domain Criteria (RDoC) provides a translational framework for identifying transdiagnostic psychiatric symptoms, but its application in perinatal affective disorders (PNAD) is yet limited. Here, we identified RDoC-based transdiagnostic features of PNAD in 140 primarily low-income Black and Hispanic women at 272 total longitudinal visits across the perinatal period. Women completed RDoC self-report measures of potential threat and reward valuation-Behavioral Inhibition System/Behavioral Activation System scale (BIS/BAS) and Intolerance of Uncertainty Scale (IUS)-and measures of depression (Patient Health Questionnaire-9; PHQ-9) and anxiety (Generalized Anxiety Disorder-7; GAD-7). Longitudinal mixed effects models assessed associations of between-person ("trait-like") and within-person ("state-like") measures of potential threat (BIS/IUS) and reward valuation (BAS-Drive) with depression and anxiety symptoms. Higher "trait-like" BIS (standardized b = 2.33, p < .001) and IUS (b = 2.97, p < .001) scores, higher "state-like" BIS (b = .71, p < .001), and lower "state-like" BAS-Drive (b = - .58, p = .04) scores were associated with worse depressive symptoms. Higher "trait-like" BIS (b = 2.22, p < .001) and IUS (b = 2.73, p < .001) and higher "state-like" BIS scores (b = .92, p < .001) were associated with worse anxiety symptoms. Potential threat may be a prominent, transdiagnostic feature of perinatal anxiety and depression, whereas reward valuation may be a non-transdiagnostic, weaker feature of perinatal depression. Potential threat is important as both a "trait-like" feature that is sustained across the perinatal period and a "state-like" feature that varies within a woman across pregnancy. Grounded in RDoC, this work reveals neurobiological targets for translational research into PNAD.

Using computerised adaptive tests to screen for perinatal depression in underserved women of colour.

BACKGROUND: Compared with traditional screening questionnaires, computerised adaptive tests for severity of depression (CAT-DI) and computerised adaptive diagnostic modules for depression (CAD-MDD) show improved precision in screening for major depressive disorder. CAT measures have been tailored to perinatal women but have not been studied in low-income women of colour despite high rates of perinatal depression (PND). OBJECTIVE: This study aimed to examine the concordance between CAT and traditional measures of depression in a sample of primarily low-income black and Latina women. METHODS: In total, 373 women (49% black; 29% Latina) completed the Patient Health Questionnaire-9 (PHQ-9), CAD-MDD and CAT-DI at 845 visits across pregnancy and postpartum. We examined the concordance between continuous CAT-DI and PHQ-9 scores and between binary measures of PND diagnosis on CAD-MDD and the PHQ-9 (cut-off score >10). We examined cases with a positive PND diagnosis on the CAD-MDD but not on the PHQ-9 ('missed' cases) to determine whether clinic notes were consistent with CAD-MDD results. FINDINGS: CAT-DI and PHQ-9 scores were significantly associated (concordance correlation coefficient=0.67; 95% CI 0.58 to 0.74). CAD-MDD detected 5% more case of PND compared with PHQ-9 (p<0.001). The average per-visit rate of PND was 14.4% (14.5% in blacks, 14.9% in Latinas) on the CAD-MDD, and 9.5% (9.8% in blacks, 8.8% in Latinas) on the PHQ-9. Clinical notes were available on 60% of 'missed' cases and validated CAD-MDD PND diagnosis in 89% of cases. CONCLUSIONS: CAD-MDD detected 5% more cases of PND in women of colour compared with traditional tests, and the majority of these cases were verified by clinician notes. CLINICAL IMPLICATIONS: Use of CAT in routine clinic care may address health disparities in PND screening.

Neuroactive steroids and depression in early pregnancy.

Progesterone (P4) can be metabolized to two general classes of neuroactive steroids (NAS) -those like allopregnanolone (ALLO) and pregnanolone (PA) which are positive allosteric modulators of the Gamma Aminobutyric Acid type A (GABAA) receptor and those like isoallopregnanolone (ISOALLO) and epipregnanolone (EPI) which are negative allosteric modulators of the GABAA receptor. While exogenous administration of ALLO is effective in treating postpartum depression, knowledge gaps remain in the dynamic interplay of NAS across the perinatal period. In particular little is known about ALLO and PA in relation to depression earlier in pregnancy, and the role of ISOALLO and EPI in relation to depression at any point in the perinatal period. In a prospective, nested case/control study in low-income women of color, we compared the metabolism of P4 to four NAS (i.e., ratios ALLO:P4, PA:P4, ISOALLO:P4, EPI:P4) in pregnant women with depression at either or both of the first and second trimesters (cases) and women without depression at either time point (controls). Fifty women (36% depressed, 56% Black, 28% Latina) completed depression screening using a computerized adaptive test of mental health (CAT-MH™) and provided blood serum samples in both trimesters. In longitudinal mixed effects models of both trimesters, PND cases showed higher ratios of ALLO:P4 (p = .002) and PA:P4 (p = .03) compared to controls. In regression models of only first trimester data, there was no significant difference in NAS ratios between cases and controls (p > .05). Conversely, in models of the second trimester, ratios of PA:P4 (p = .002) and ISOALLO:P4 (p = .01) were significantly higher in cases compared to controls, and ratios of ALLO:P4 (p = .08) and EPI:P4 (p = .1) also trended higher in cases. The most severe cases, those with depression at both trimesters, showed an increase in ALLO:P4 (p = .06) and EPI:P4 (p < .001) ratios from the first to the second trimester, whereas controls showed a decrease in these ratios. Secondary analyses confirmed higher levels of ALLO (p = .04) and PA (p = .07) overall in cases compared to controls, along with higher levels of PA (p = .005) and ISOALLO (p = .02) in the second trimester alone. This work suggests a dynamic relationship between NAS and PND; whereas low ALLO levels have been previously associated with postpartum depression, earlier in pregnancy a higher metabolism of P4 to ALLO (and higher ALLO levels) is associated with depression. Some women may show a hormone-sensitive depressive response to acute increases in NAS metabolism in early pregnancy.

Depression and anxiety symptoms across pregnancy and the postpartum in low-income Black and Latina women.

Underserved women of color experience high rates of perinatal affective disorders, but most research to date on the natural history of these disorders has been conducted on White women. The present study investigated longitudinal changes in anxiety and depression in a sample of perinatal non-Hispanic Black and Latina women. Categorical (yes/no) measures of positive anxiety and depression screens, as well as total symptom scores, were measured longitudinally across the perinatal period in 178 women (115 non-Hispanic Black, 63 Latina) using the CAT-MH™, a computerized adaptive test. Time (up to 4 visits) and race/ethnicity effects were assessed in linear mixed effects models. Rates of positive anxiety screenings were 13.6%, 3.2%, 8.5%, and 0% in Latina women and 2.6%, 4.2%, 6.1%, and 5.8% in non-Hispanic Black women in the 1st, 2nd, and 3rd trimesters, and postpartum, respectively. Rates of positive anxiety screenings overall were highest in the first trimester (OR = 0.20; 95% CI 0.04-0.98), and there was a significant time-by-race/ethnicity interaction for positive anxiety screens (OR = 8.88; 95% CI 1.42-55.51), as positive screens were most frequent in the first trimester and sharply declined for Latina women, while rates were relatively consistent across the perinatal period in non-Hispanic Black women. Rates of positive depression screens did not change over time, but there was a trend (OR = 1.93; 95% CI 0.93-4.03) for a time-by-race/ethnicity interaction in a direction similar to that seen for anxiety. The odds of positive anxiety screens vary by race/ethnicity and trimester, suggesting that anxiety screening and anxiety interventions may be most resourcefully used in the first trimester for Latina women in particular.

Novelty Detection in Memory for Common and Uncommon Odors over Short Delays.

Odor memory is commonly believed to be very strong and long-lasting. The present study examined factors that impact odor recognition memory over short delay intervals (immediately or 30 s after target presentation) with emphasis on memory task (forced-choice vs "monadic"/single stimulus yes/no), odor category, and target/foil relationship. We explored trial-by-trial confidence as well as the effect of target familiarity, pleasantness, and intensity ratings, and odor nameability on memory for odors. Overall odor recognition memory in terms of proportion correct and sensitivity measures did not decline significantly during the 30-s delay interval in either task. However, hit rates were lower at 30 s and correct rejection rates for common odors remained consistently high. Recognition memory was better on trials in which the odor pairs were highly dissimilar, as well as on trials in which the target was an uncommon odor, particularly if it could be named. Familiarity, pleasantness, and intensity had no systematic effect on recognition memory. Whereas the results provide evidence of a fading memory trace, indicated by the decreased hit rates after a 30-s delay, the constant rates of correct rejections and high confidence ratings on those trials, even after delay, suggests that novelty detection (i.e., recognition that an odor is not one that has been encountered previously in that context) may play an important role in the memory for odors over short delays. Whether there is a separate short-term odor memory store is also addressed.

An Evidence-Based Walking Program in Oregon Communities: Step It Up! Survivors.

Physical activity can help mitigate the long-term symptoms and side effects of cancer and its treatment, but most cancer survivors are not active enough to achieve these benefits. An evidence-based strategy to promote physical activity among adults is a community group-based walking program. However, many evidence-based programs do not achieve intended population health outcomes because of the challenges of real-world implementation. We used the Interactive Systems Framework for Dissemination and Implementation to conceptualize implementation of a capacity-building intervention to support delivery of a community group-based walking program. We adapted an evidence-based guide for community group-based walking programs for cancer survivors and their support network. We provided a capacity-building intervention (technical assistance and small-grant funding) and evaluated this implementation intervention. We assessed effectiveness of the intervention by measuring adoption, acceptability, appropriateness, feasibility, fidelity, implementation costs, and penetration through monthly progress reports, site visit observations, interviews, and a final report. Eight organizations received a small grant and technical assistance and implemented Step It Up! Survivors (SIUS). SIUS helped cancer survivors increase their physical activity, establish social connections, and be part of a supportive environment. Despite receiving monthly technical assistance, some grantees experienced challenges in recruiting participants, developing community partnerships, and adhering to the prescribed implementation plan. Implementation facilitators included community partners and specific components (eg, incentives for participants, webinars). Organizations needed different amounts and types of assistance with adaptation and implementation. Overall fidelity to SIUS ranged from 64% to 88%. Some integrated SIUS within existing organizational programming for sustainability. The provision of funding and technical assistance was a successful implementation intervention. Our results suggest a need to better tailor technical assistance while organizations are in the process of adapting, implementing, and sustaining an evidence-based program in their local communities.

Cell-cycle Checkpoints and Aneuploidy on the Path to Cancer.

The cell cycle is a complex sequence of events through which a cell duplicates its contents and divides, and involves many regulatory proteins for proper cellular reproduction, including cyclin proteins and cyclin-dependent kinases, oncogenes and tumor-suppressor genes, and mitotic checkpoint proteins. Mutations of any of these regulatory mechanisms can lead to reproduction of cells carrying genetic mutations or abnormal numbers of chromosomes, resulting in genomic instability. Chromosomal instability, contributing to genomic instability, refers to abnormalities in the number of chromosomes, and leads to aneuploidy. The role of aneuploidy in cancer cell development is often disputed, as conflicting hypotheses and research make it unclear as to whether aneuploidy is a cause or consequence of cancer. Here, we present an overview of the importance of cell-cycle checkpoint regulation and chromosomal instability in the development of cancer, and discuss evidence for conflicting arguments for the role of aneuploidy in cancer, leading us to conclude that further investigation of this role would benefit our understanding of cancer development.

Neural mechanisms of affective interference in schizotypy.

Negatively valenced stimuli foster cognitive impairment in schizotypy and schizophrenia. To identify relevant brain mechanisms, the authors had 16 positive-schizotypy and 16 control participants perform an emotional Stroop task, judging the ink color of negative and neutral words during functional magnetic resonance imaging (fMRI) of regional brain activity. Schizotypy individuals showed increased right and decreased left activity in dorsolateral prefrontal cortex, indicating a deficit in maintenance of attentional set in the presence of negative emotional distractors. They also showed abnormal activity in ventral limbic areas, including decreased activity in nucleus accumbens and increased activity in hippocampus and amygdala, a circuit involved in the integration of cognitive and affective processes. These results indicate that aspects of emotion-cognition processes and the brain mechanisms that implement them are similar in schizotypy and schizophrenia.